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Genotype-phenotype Correlation Study of Presymptomatic and Symptomatic DFNA9 Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03716908
Recruitment Status : Recruiting
First Posted : October 23, 2018
Last Update Posted : October 23, 2018
Maastricht University Medical Center
Information provided by (Responsible Party):
Jessa Hospital

Brief Summary:
DFNA9 (Deafness Autosomal Dominant 9) is an autosomal dominant hereditary hearing loss which is associated with vestibular deterioration. The most recent genotype-phenotype correlation studies have been conducted more than 10 years ago. Meanwhile, emerging and valuable vestibular tests have been added to the vestibular test battery. These tests were not available at the time of the correlation studies. The aim of this study is to carry out a prospective cross-sectional study on symptomatic and presymptomatic affected carriers of the Pro51Ser (P51S) Coagulation Factor C Homology (COCH) mutation in order to correlate vestibular data using the complete vestibular test battery with the known data on hearing and vestibular function in relation to age.

Condition or disease
Vestibular Diseases DFNA9

Detailed Description:

Systematic review of the genotype-phenotype correlation studies in P51S carriers has shown an underrepresentation of presymptomatic affected subjects and the calculation of vestibular deterioration were based on just one vestibular parameter, whereas the combined evaluation of a complete vestibular test battery, covering the whole range of vestibular sensitivity components is nowadays considered standard practice in determining more accurate assessment of the vestibular function.

For this reason, a prospective cross-sectional study on pre- as well as symptomatic DFNA9 patients carrying the Pro51Ser (P51S) mutation in COCH gene is being carried out, in order to gain more realistic data on vestibular dysfunction, consisting of pure tone audiometry and a comprehensive vestibular test battery, including electro- or videonystagmography (VNG), C- and O-Vestibular evoked myogenic potential (VEMP) tests, video Head Impulse Test (vHIT) and questionnaires (DHI (Dizziness handicap Index), oscillopsia questionnaire (OS), Quality of Life Questionnaire (EQ-5D-5L), activities-specific balance confidence (ABC) scale.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 70 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Target Follow-Up Duration: 1 Year
Official Title: Evaluation of Hearing and Vestibular Function in Presymptomatic and Symptomatic DFNA9 Patients Carrying the Pro51Ser (P51S) Mutation in the COCH Gene.
Actual Study Start Date : June 1, 2018
Estimated Primary Completion Date : March 30, 2019
Estimated Study Completion Date : November 30, 2019

P51S+ group

Group 1 affected subjects (P51S+) Family member P51S mutation carrier

interventions/ Questionnaire (DHI, OS, EQ-D5-5L, ABC) Pure Tone audiometry VNG vHIT c- and o-VEMP

P51S- group (healthy control)

Group 2: healthy control Family member P51S non-carrier

interventions: Questionnaire (DHI, OS, EQ-D5-5L, ABC) Pure Tone audiometry VNG vHIT c- and o-VEMP

Primary Outcome Measures :
  1. hearing threshold [ Time Frame: 1 year ]
    pure tone audiometry, decibel hearing loss (dB HL)

  2. video HIT [ Time Frame: 1 year ]
    video Head Impulse test, gain (degrees per second)

Secondary Outcome Measures :
  1. VEMP [ Time Frame: 1 year ]
    c- and o-VEMP tests (vestibular evoked myogenic potentials): threshold (decibel sound pressure level: dB SPL)

  2. DHI questionnaire [ Time Frame: 1 year ]
    DHI (dizziness handicap index): scores the degree of imbalance perception of the patient, the higher the score, the higher the imbalance perception; normative score below 10

  3. OS questionnaire [ Time Frame: 1 year ]
    A questionnaire assessing oscillopsia severity for patients with bilateral vestibulopathy and patients with unilateral vestibular lesions. Oscillopsia was defined as a "sensation that the isual environment is moving when it's not." The 9-item questionnaire investigates oscillopsia frequency in different situations encountered in daily life. Each item was scored 1 (never), 2 (seldom), 3 (sometimes), 4 (often), or 5 (always). Scores were averaged to provide an oscillopsia severity score ranging from 1 to 5. A mean score higher than 3 is considered to indicate moderate to extreme oscillopsia severity.

  4. ABC questionnaire [ Time Frame: 1 year ]
    ABC activities specific balance confidence scale to asses individual's confidence in performing daily activities , scores from 0-100%, normative values >80%, Powel et al.1995

  5. EQ-5D-5L questionnaire [ Time Frame: 1 year ]
    Quality of life questionnaire:EQ-5D is a standardised measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal; 5 dimensions: anxiety/depression, discomfort/pain, usual activities, mobility and self-care are evaluated in 5 levels (ranging from no problems (level 1) to extreme problems (level 5) and a Vertical Visual Analogue Scale (VAS) EQ-VAS ranging from 0 (worst health) to 100 (best health), convertible to an index value. result presentation in EQ-5D (dimensions), EQ-VAS and EQ-5D-5L index values with normative values per age group, all as a measure of central tendency and a measure of dispersion using mean values and standard deviation per age group

  6. Caloric response [ Time Frame: 1 year ]
    Caloric response using 4 successive water irrigation at 30 and 44 degrees Celsius , summation of the gain of the slow phase of the elicited nystagmus af all 4 irrigations (degrees per second) , normative values to be estiablished for each vestibular laboratory in healthy control subjects

  7. SHAT [ Time Frame: 1 year ]
    Sinusoidal harmonic acceleration test (SHAT) of rotatory chair in the dark with open eyes, degrees per second, normative values to be established for each vestibular laboratory on healthy control subjects

Biospecimen Retention:   Samples With DNA
blood samples for the genetic diagnosis of carriership of P51S COCH mutation

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
all family pedigree in which at least one proband is carrying the Pr51Ser (P51S) mutation in the COCH gene that are known in three tertiary referral centers: University Hospital Antwerp, Maastricht University Medical Centre and Jessa Hospital Hasselt.

Inclusion Criteria:

  • subject must be 18 year of older
  • subject is a family member of the family pedigree's proband(s) carrying a P51S COCH mutation

Exclusion Criteria:

  • subject is younger than 18 years
  • subject is not a family member of the pedigree's proband(s) carrying a P51S
  • subject cannot undergo investigations (medical and/or mental reasons)
  • subject is not willing to be enrolled into the study
  • subject suffers other concomitant middle or inner ear disease
  • subject has undergone middle ear or inner ear surgery
  • subject suffers other concomitant vestibular disease than DFNA9
  • subject has undergone vestibular surgery or other non-invasive vestibular treatment (gentamicin intratympanal injections for example)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03716908

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Contact: sebastien PF JanssensdeVarebeke, MD 011337420
Contact: Vincent Van Rompaey, PhD, MD 038213385

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University of Antwerp Recruiting
Antwerpen, Belgium, 2650
Contact: Vincent Van Rompaey, PhD, MD    038213385   
Principal Investigator: sebastien PF JanssensdeVarebeke, MD         
Sponsors and Collaborators
Jessa Hospital
Maastricht University Medical Center

Additional Information:

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Responsible Party: Jessa Hospital Identifier: NCT03716908     History of Changes
Other Study ID Numbers: JessaHORL2
First Posted: October 23, 2018    Key Record Dates
Last Update Posted: October 23, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Vestibular Diseases
Labyrinth Diseases
Ear Diseases
Otorhinolaryngologic Diseases